An effective therapy for both undifferentiated (including Burkitt's) lymphomas and lymphoblastic lymphomas in children and young adults

Abstract

We have used a single intensive chemotherapy regimen in the treatment of young patients with diffuse, aggressive, malignant lymphomas. There were two major histologic types of lymphoma in our series: lymphoblastic lymphomas, which presented most often with mediastinal tumor (64%), and undifferentiated lymphomas (mostly Burkitt’s lymphomas), which occurred predominantly in the abdomen (86%). Our objective was to examine the determinants of prognosis in a uniformly treated patient group that included 31 children (2–16 yr) and 34 young adults 17–35 yr). Patients with extensive bone marrow involvement (greater than 50% replacement by tumor cells) were included in the study. Treatment consisted essentially of a 4-drug combination (cytoxan, adriamycin, vincristine, and prednisone) alternating with a 42-hr methotrexate infusion, followed by leukovorin rescue, and included intrathecal prophylactic therapy against central nervous system (CNS) disease. Patients with localized or resected undifferentiated lymphoma received 6 therapy cycles; all other patients received 15 cycles. Radiation therapy was used only in exceptional circumstances. Fifty-eight of 65 patients (89%) achieved complete remission: 97% of children and 82% of adults. The estimated 3-yr survival was 60% (SE 6.4%) with a median follow-up of 3 yr. Analysis of factors associated with remission duration and survival indicated that bone marrow involvement at referral and extensive disease were poor prognostic variables. Patients with lymphoblastic lymphomas and patients with completely resected undifferentiated lymphomas had the best prognosis (81% +/- 12% and 94% +/- 6% estimated 3-yr survival, respectively). Patients with extensive intraabdominal undifferentiated lymphoma (stage D) had the worst prognosis (33% +/- 11% estimated 3 yr survival), but even in this subgroup, bone marrow involvement was an adverse factor (estimated survival in stage D patients with and without bone marrow involvement was 14% +/- 13% and 43% +/- 15%, respectively). Elevated uric acid and/or lactic dehydrogenase (LDH) were also of prognostic significance, but predominantly reflected state, i.e., extent of disease. Age did not significantly influence prognosis. In the undifferentiated lymphoma subgroup, histology (i.e., Burkitt's lymphoma versus non-Burkitt’s lymphoma) was not of prognostic significance. Total white count was below 1,000/cu mm in 39% of cycles, and fever associated with granulocytopenia occurred in 17% of cycles. Stomatitis of moderate to severe extent occurred in 50% of cycles.(ABSTRACT TRUNCATED AT 400 WORDS)

RD‐CODOX‐M/IVAC with rituximab and intrathecal liposomal cytarabine in adult Burkitt lymphoma and ‘unclassifiable’ highly aggressive B‐cell lymphoma

“…The outcome of these diseases has been reported to be generally poor after treatment with front‐line regimens specifically designed for DLBCL (Dave et al , 2006; Nomura et al , 2008; Smeland et al , 2004), whereas chances of cure up to 70% hinge upon the use of more intense and rapidly recycling multi‐agent chemotherapy, coupled with aggressive intrathecal (IT) and systemic prophylaxis for central nervous system (CNS) disease (Blum et al , 2004; Hoelzer, 2009; Kasamon & Swinnen, 2004; Nomura et al , 2008). This strategy, borrowed from paediatric literature, is aimed at countering rapid tumour regrowth/spreading between chemotherapy courses, avoiding early emergence of chemoresistant clones, and preventing the risk, which is expected to be high, for CNS (predominantly leptomeninges) involvement (12–17%) and recurrence (6–11% and 30–50%, with and without IT chemoprophylaxis, respectively) (Bernstein et al , 1986; Hill & Owen, 2006; Magrath et al , 1984; Sariban et al , 1983). Recent studies suggest that this approach can be implemented by targeting the strong expression of the B‐cell lineage restricted marker, CD20, on tumour cells of BL and BL/DLBCL, and have reported promising results by the addition of the monoclonal anti‐CD20 antibody rituximab to an abbreviated‐intensive regimen in human immunodeficiency virus (HIV)‐positive adults and patients older than 60 years of age (Oriol et al , 2008; Thomas et al , 2006).…”

“…Modified versions were subsequently developed for older patients to ensure a safer toxicity profile while maintaining the original alternating sequence of CODOX‐M and IVAC courses with fractionated schedule of alkylators, high‐dose CNS‐penetrating agents, and IT cytarabine/MTX injections for CNS prophylaxis (Lacasce et al , 2004; Mead et al , 2008, 2002). This latter CNS‐directed programme has been regarded as a critical component of the strategy against these tumours because, when given only as high‐dose intravenous (iv) load, cytarabine and MTX were unable to abrogate completely the risk of early leptomeningeal recurrences (Jabbour et al , 2005; Magrath et al , 1984). However, since cytarabine and MTX are cell‐cycle S‐phase‐specific agents with short terminal half‐lives (3·4 and 4·5 h, respectively), repeated IT courses are needed, 8–11 for CODOX‐M/IVAC (Magrath et al , 1996) and 10–16 for other treatment platforms (Divine et al , 2005; Thomas et al , 1999), to warrant sustained cytotoxic concentrations in the cerebrospinal fluid (CSF) (Fleischhack et al , 2005; Shapiro et al , 1975).…”

Minimally Invasive Treatment of Sporadic Burkitt’s Lymphoma Causing Ileocaecal Invagination

“…The surgical treatment in Burkitt's lymphoma intussusception due to localized disease consists in resection and anastomosis of the pathological tract [ 24 ]. On the other hand, Magrath et al, considering a study in Burkitt's lymphoma patients in Uganda, suggest that an aggressive operative debulking, with a tumor removal of 90%, performed before the chemotherapy may increase survival [ 25 ].…”

Non-Hodgkin's lymphomas in childhood a clinicopathologic and epidemiologic study in finland

“…When histologic sections are of good quality the differentiation between LBL and BL does not usually cause problems. The following histologic criteria have been presented for this differential diagnosis: (1) definite cytoplasmic MGP-positivity (or basophilia in Giemsa stain) in BL, but only weak or no staining in LBL; (2) smaller amount of cytoplasm in LBL than in BL; (3) usually a cohesive growth pattern in BL, but often somewhat overlapping nuclei in LBL; (4) moderately prominent nucleoli in BL, but small nucleoli in LBL; (5) roundish nuclei in BL, but usually convoluted nuclei in LBL; (6) in BL slightly larger nuclei than in LBL; (7) tumor necrosis sometimes in BL, but rarely in LBL; (8) a starry sky pattern usually in BL, but less commonly in LBL; and (9) in early involvement of a lymph node, preserved lymphatic follicles within the tumor tissue often in LBL but practically never in BL.…”